Salsolinol

Structural formula
1: 1 mixture of ( S ) -form (top) and ( R ) -form (bottom)
General
Surname	Salsolinol
other names	1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline ( IUPAC )
Molecular formula	C 10 H 13 NO 2 [salsolinol] C 10 H 13 NO 2 · HBr [salsolinol · hydrobromide]
Brief description	gray solid
External identifiers / databases
CAS number 525-72-4 [( RS ) -Salsolinol] 27740-96-1 [( S ) -Salsolinol] 53622-83-6 [( R ) -Salsolinol] 59709-57-8 ([( RS ) -Salsolinol · hydrobromide ]) 70681-20-8 ([( RS ) -Salsolinol · hydrochloride ]) PubChem 54456 Wikidata Q2215280
properties
Molar mass	179.22 g · mol -1 [salsolinol]
Physical state	firmly
Melting point	186-187 ° C
solubility	very low in water
safety instructions
GHS labeling of hazardous substances Hydrobromide Caution H and P phrases H: 315-319-335 P: 261-305 + 351 + 338
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Salsolinol is an isoquinoline - alkaloid , which as a racemate with up to 25 ug / g in chocolate , cocoa and bananas can be formed but also endogenously occurring in the body. Salsolinol inhibits various enzymes , for example monoamine oxidase and tyrosine hydroxylase . It is neurotoxic at higher concentrations and has been suspected of having an important role in the pathogenesis of Parkinson's disease . Some of the causes of neurotoxicity are known. The generation of oxidative stress plays a role. At low concentrations, salsolinol appears to have neuroprotective properties. Salsolinol is a metabolite of ethanol and as such is partly responsible for its intoxicating effect.

Importance as an ethanol metabolite

After ingestion of ethanol, salsolinol is formed from acetaldehyde in the body. H. the first metabolic oxidation product of ethanol, and the neurotransmitter dopamine .

Both enantiomers of salsolinol are functionally selective agonists at the μ-opioid receptor in that they activate the signal path via the G protein, but not via the β-arrestin. With an EC ₅₀ of 20 μM, the potency of the racemate is significantly weaker than that of morphine (4 nM). ( S ) -Salsolinol is more effective than its counterpart (EC ₅₀ = 9 μM versus 600 μM). Morphine and salsolinol occupy the same binding site on the receptor and occupy the same position.

synthesis

Salsolinol is synthesized biochemically from dopamine and pyruvate . The biochemical synthesis is catalyzed by the enzyme salsolinol synthase . This creates ( R ) - (+) - salsolinol.

Both physiologically and preparatively (e.g. in the laboratory), racemic ( RS ) salsolinol is formed by the condensation of dopamine with acetaldehyde according to the Pictet-Spengler reaction .

Stereoisomerism

Salsolinol is chiral and contains a stereocenter. So there are two enantiomers , the ( S ) -Salsolinol and the ( R ) -Salsolinol. The enantiomers have different cytotoxicity: ( S ) -Salsolinol is more cytotoxic (IC ₅₀ = 67 μmol l ⁻¹ ) than ( R ) salsolinol (IC ₅₀ = 167 μmol l ⁻¹ ).

Individual evidence

1. ↑ ^{a b} Salsolinol data sheet at Acros, accessed on February 19, 2010.
2. ↑ ^{a b c} Data sheet 1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrobromide from Sigma-Aldrich , accessed on May 9, 2017 ( PDF ).
3. ^ ^{A b} M. F. Melzig, I. Putscher, P. Henklein, H. Haber: In vitro pharmacological activity of the tetrahydroisoquinoline salsolinol present in products from Theobroma cacao L. like cocoa and chocolate , in: Journal of Ethnopharmacology , 2000 , 73 , p 153-159. doi : 10.1016 / S0378-8741 (00) 00291-9 .
4. ↑ Entry on (R) -Salsolinol in the Human Metabolome Database (HMDB) , accessed on September 25, 2013.
5. ↑ Naoi M, Maruyama W, Akao Y, Zhang J, Parvez H: Apoptosis induced by an endogenous neurotoxin, N-methyl (R) salsolinol, in dopamine neurons . In: Toxicology . 153, No. 1-3, 2000, pp. 123-41. PMID 11090952 .
6. ↑ JH Kang: Salsolinol, a tetrahydroisoquinoline catechol neurotoxin, induces human Cu, Zn-superoxide dismutase modification  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. , in: J. Biochem. Mol. Biol. , 2007 , 40 (5) , pp. 684-689 ( PMID 17927901 ).  
7. ↑ Kim SS, Kang JY, Kang JH: Oxidative modification of human ceruloplasmin induced by a catechol neurotoxin, salsolinol . In: BMB Rep . 49, No. 1, 2016, pp. 45-50. PMID 26077029 . PMC 4914212 (free full text).
8. ↑ Kang JH: Salsolinol, a catechol neurotoxin, induces oxidative modification of cytochrome c . In: BMB Rep . 46, No. 2, 2013, pp. 119-23. PMID 23433116 . PMC 4133855 (free full text).
9. ↑ Możdżeń E, Kajta M, Wąsik A, Lenda T, Antkiewicz-Michaluk L: Salsolinol, an endogenous compound triggers a two-phase opposing action in the central nervous system . In: Neurotox Res . 27, No. 3, 2015, pp. 300-13. doi : 10.1007 / s12640-014-9511-y . PMID 25537852 . PMC 4353863 (free full text).
10. ↑ Deehan GA, Brodie MS, Rodd ZA: What is in that drink: the biological actions of ethanol, acetaldehyde, and salsolinol . In: Curr Top Behav Neurosci . 13, 2013, pp. 163-84. doi : 10.1007 / 7854_2011_198 . PMID 22351424 . PMC 4955731 (free full text).
11. ↑ Berríos-Cárcamo P, Quintanilla ME, Herrera-Marschitz M, Vasiliou V, Zapata-Torres G, Rivera-Meza M: Racemic Salsolinol and its Enantiomers Act as Agonists of the μ-Opioid Receptor by Activating the Gi Protein-Adenylate Cyclase Pathway . In: Front Behav Neurosci . 10, 2016, p. 253. doi : 10.3389 / fnbeh.2016.00253 . PMID 28167903 .
12. ↑ MF Melzig, I. Putscher, H. Haber, M. and J. Rottmann Zipper: Toxicity and Pharmacological Effects of Salsolinol in Different Cultivated Cells in A. Moser: Pharmacology of Endogenous neurotoxin, published by Birkhauser Boston (1998), ISBN 978- 0-8176-3993-8 , p. 253.